The intramolecular condensation reaction named after Dieckmann (Ber. Dtsch. Chem. Ges. 1894 (27) 965, Liebigs Ann. 1901 (317) 27) is known. For example, the Dieckmann condensation of dialkyl adipates leads to alkyl cyclopentanone-2-carboxylates. The process is based on a condensation reaction in which the respective alcohol is liberated:

In these processes, the alkali metal salt or the alkaline earth metal salt of the desired compound is prepared with virtually quantitative conversion and selectivity and this salt is worked up under acid conditions in a further step. Many attempts to optimize the procedure and the yield of this reaction have been discussed in the literature. These relate to both the condensation agent to be used and the process methodology and solvents used.
For example, the cyclization of adipic esters by reaction with stoichiometric amounts of a strong Lewis acid (e.g. AlCl3, TiCl2(OTf)2) and a base (e.g. NEt3) as condensation agent has been described (e.g. Pecanha et al., Quim. Nova 20 (1997) 435; Tanabe et al., Chem. Lett. (1986) 1813). Here, the reaction takes place in solution in good yields, but stoichiometric amounts of Lewis acid and base (e.g. triethylamine) have to be used. In the subsequent aqueous work-up, the Lewis acid used is completely hydrolysed, which is undesirable from economic and ecological points of view.
In addition, many processes which bring about the cyclization by means of a strong base as condensation agent have been described. Suitable bases are, for example, alkali metals (e.g. Pinkney, Org. Synth. 1937 (17) 32), metal hydrides (e.g. Bloomfield et al., Tetrahedron Lett. 1964, 2273) or metal amides (e.g. Bouveault et al., Compt. Rend. 146 (1908) 138).
It has been found to be particularly useful to use alkoxides, in particular alkoxides of the alkali metals and alkaline earth metals, as bases (e.g. sodium ethoxide, Reed et al. J. Chem. Soc. 1954, 2148, or magnesium ethoxide, Laukkanen, Chem. Ber. 1957 (31) 124). The alkoxide is usually introduced into the reaction as a solution in the corresponding alcohol. To avoid transesterification of the starting material for the reaction or the reaction product by the alkoxide used or the alcohol used, it is usual to employ materials having an identical substitution pattern for the Dieckmann cyclization. (Methoxides in methanol for the cyclization of methyl esters, ethoxides in ethanol for the cyclization of ethyl esters, etc.). The alkoxides required are obtained either by reaction of the corresponding metal with the alcohol or by dewatering of alcoholic sodium hydroxide or potassium hydroxide.
Since Dieckmann reactions are equilibrium reactions, it is necessary to remove the alcohol liberated during the reaction and also the alcohol used as solvent quantitatively in order to achieve a quantitative conversion. A Dieckmann reaction is therefore usually carried out in nonpolar solvents such as toluene or xylene and the alcohol is distilled off.
The literature methods for Dieckmann cyclization using alkoxides in nonpolar solvents have various disadvantages for economical industrial use. A particular problem is that a viscous suspension comprising the starting materials for the reaction, the salt of the reaction product and the solvent is formed during the reaction and this can be stirred only with great difficulty from an industrial point of view. Only a low space-time yield can be achieved by means of this reaction, since it has to be carried out in a very dilute suspension which typically comprises only about 10–20% by weight of reactants and 80–90% by weight of solvent in order for the suspension to remain stirrable.
Furthermore, owing to the high viscosity of the mixture, it is usually not possible to bring about complete conversion, i.e. 100% reaction of the adipic ester, in an acceptable time. In this case, a product which still contains amounts of starting material is obtained after hydrolysis of the reaction mixture. This starting material can be separated off from the desired cyclic alkyl ketonecarboxylate by distillation only with great difficulty, since the substances have similar boiling points.
The use of various solvents which reduce the viscosity of the reaction mixture and are said to enable the Dieckmann cyclization to be carried out more easily as a result has been described.
Cassebaum et al. (DD-A 085560 (1971); Z. Chem. 1971 (11) 14) describe a process in which the reaction with sodium ethoxide as base is carried out in a solvent mixture of o-dichlorobenzene and dimethylformamide.
Richter Gedeon (HU-A 173512, 1978) likewise describe a process in which dipolar, aprotic solvents (e.g. dimethylformamide) are used for Dieckmann reactions.
Kao Corp (JP-A 9183755, 1997) carries out the reaction in solvent mixtures of aromatic organic solvents (e.g. toluene, xylene) and in tertiary alcohols (e.g. tert-butanol, amyl alcohol). The corresponding tertiary alkoxides as condensation agents are produced by reaction of the tertiary alcohol with sodium or sodium hydride.
Processes in the presence of a solvent have various disadvantages. The separation and recovery of the alcohol from the solvents used is complicated. Water present in the solvents used reacts with the strong bases used and decomposes them. Polar solvents or solvent mixtures are somewhat expensive and difficult to regenerate. They are completely or partially miscible with water, so that the polar solvent or the polar components of the solvent mixture are dissolved in the aqueous phase during the work-up of the reaction mixture as a result of acid, aqueous hydrolysis. The polar solvents can be recovered from the aqueous phase only with great difficulty. In addition, proportions of the reaction product can also be carried together with the polar solvent into the aqueous phase. When highly polar solvents or solvent mixtures are used, no phase separation occurs on hydrolysis, but instead a uniform water/solvent/product phase which can be worked up only with great difficulty is formed. The extraction with a nonpolar solvent which is necessary to recover the product from the aqueous phase and the complicated recovery of the highly polar solvent from the aqueous phase are substantial disadvantages of the methodology described.
Processes which do not use an additional solvent are therefore advantageous. VEB Fahlberg List (DE-A 2055009 (1972)) describe a process in which the reaction is carried out exclusively in the alcohol used for the synthesis of the condensation agent. For example, magnesium powder is dissolved in an excess of ethanol for the synthesis of ethyl cyclopentanone-2-carboxylate. The magnesium ethoxide formed is admixed with diethyl adipate and ethanol is distilled off, forming a resin-like mass.
This process has various disadvantages. The use of a solvent continues to be necessary. The quantitative removal of the alcohol necessary for a quantitative conversion is possible only under drastic conditions; the mixture is heated to about 220° C. for 1¾ to 2½ hours at a batch size of 1.6 mol. This procedure is unsuitable for production on an industrial scale. In the further course of the process disclosed, the resin-like mass has to be dissolved in benzene before hydrolysis. The use of additional solvents is therefore still necessary during the course of the process. Only 90% of the benzene used can be recovered.
Processes in which alcohol for dissolving the condensation agent can also be dispensed with are therefore particularly advantageous. Toda et al. (J. Chem. Soc., Perkin Trans. 1, 1998/3521) describe a method in which an alcohol for dissolving the alkoxide used is also dispensed with. Here, the dialkyl adipate is triturated with a solid alkali metal alkoxide in a pestle and mortar. The reaction product is set free from the salt by addition of p-toluenesulphonic acid. Interestingly, a quantitative conversion is not achieved in this example. A yield of 61% is reported in the reaction of diethyl adipate with sodium methoxide. A higher yield (82%) is reported when using potassium tert-butoxide as condensation agent.
This method has various disadvantages for use on an industrial scale. Costly condensation agents (e.g. sodium ethoxide) give only moderate yields. Based on the size of the batches, the specific mechanical energy introduced via the pestle is considerable.
It was therefore an object of the invention to find a technically simple process which allows the preparation of alkyl cyclopentanone-2-carboxylates with a low economic outlay while completely dispensing with solvents and at the same time resulting in complete reaction of the alkyl adipate.